Trial Outcomes & Findings for Effects of Continuous Positive Airway Pressure (CPAP) on Glucose Metabolism (NCT NCT01503164)

Results Overview

Insulin sensitivity will be determined with the insulin-modified frequently sampled intravenous glucose tolerance test (IVGTT) before and 2-months after study intervention. This test requires administration of a weight-adjusted dose of D50W as an IV bolus at time "zero". After the glucose bolus, blood samples are drawn at the scheduled times for 3-hours. At the 20-minute mark, a weight-adjusted dose of regular insulin is administered. The resulting serum is analyzed for glucose and insulin and the "minimal model" (MINMOD) will be used to derive insulin sensitivity. A low SI signifies low insulin sensitivity and high SI represents high insulin sensitivity.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

111 participants

Primary outcome timeframe

Baseline

Results posted on

2017-10-19

Participant Flow

Participant milestones

Participant milestones
Measure	Positive Pressure Therapy (PAP) Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Overall Study STARTED	55	56
Overall Study COMPLETED	53	55
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Positive Pressure Therapy (PAP) Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

Effects of Continuous Positive Airway Pressure (CPAP) on Glucose Metabolism

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Positive Pressure Therapy (PAP) n=53 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=55 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.	Total n=108 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	45 Participants n=5 Participants	44 Participants n=7 Participants	89 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants
Age, Continuous	54.8 years STANDARD_DEVIATION 9.2 • n=5 Participants	57.2 years STANDARD_DEVIATION 8.2 • n=7 Participants	56.0 years STANDARD_DEVIATION 8.8 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	39 Participants n=7 Participants	80 Participants n=5 Participants
Region of Enrollment United States	53 Participants n=5 Participants	55 Participants n=7 Participants	108 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline

Population: 55 randomized to PAP (2 dropout); 56 randomized to lifestyle (1 dropout)

Insulin sensitivity will be determined with the insulin-modified frequently sampled intravenous glucose tolerance test (IVGTT) before and 2-months after study intervention. This test requires administration of a weight-adjusted dose of D50W as an IV bolus at time "zero". After the glucose bolus, blood samples are drawn at the scheduled times for 3-hours. At the 20-minute mark, a weight-adjusted dose of regular insulin is administered. The resulting serum is analyzed for glucose and insulin and the "minimal model" (MINMOD) will be used to derive insulin sensitivity. A low SI signifies low insulin sensitivity and high SI represents high insulin sensitivity.

Outcome measures

Outcome measures
Measure	Positive Pressure Therapy (PAP) n=53 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=55 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Insulin Sensitivity (SI)	1.95 [mU/L]^-1 x [min]^-1 Standard Deviation 1.21	2.22 [mU/L]^-1 x [min]^-1 Standard Deviation 1.45

PRIMARY outcome

Timeframe: 2 months after intervention

Population: 55 randomized to PAP (2 dropout); 56 randomized to lifestyle (1 dropout)

Insulin sensitivity will be determined with the insulin-modified frequently sampled intravenous glucose tolerance test (IVGTT) before and 2-months after study intervention. This test requires administration of a weight-adjusted dose of D50W as an IV bolus at time "zero". After the glucose bolus, blood samples are drawn at the scheduled times for 3-hours. At the 20-minute mark, a weight-adjusted dose of regular insulin is administered. The resulting serum is analyzed for glucose and insulin and the "minimal model" (MINMOD) will be used to derive insulin sensitivity. A low SI signifies low insulin sensitivity and high SI represents high insulin sensitivity.

Outcome measures

Outcome measures
Measure	Positive Pressure Therapy (PAP) n=53 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=55 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Insulin Sensitivity (SI)	3.01 [mU/L]^-1 x [min]^-1 Standard Deviation 2.77	1.83 [mU/L]^-1 x [min]^-1 Standard Deviation 1.03

SECONDARY outcome

Timeframe: Baseline

Population: 55 randomized to PAP (2 dropout); 56 randomized to lifestyle (1 dropout)

Glucose effectiveness is the ability for glucose to move intracellularly in the absence of insulin. It is a parameter that results from the MINMOD analysis of the serum glucose and insulin levels derived from the frequently sampled intravenous glucose tolerance test. Low SG indicates a lower predisposition for glucose disposal independent of any effects of insulin.

Outcome measures

Outcome measures
Measure	Positive Pressure Therapy (PAP) n=53 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=55 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Glucose Effectiveness (SG)	0.01498 [min]^-1 Standard Deviation 0.006408	0.01537 [min]^-1 Standard Deviation 0.00636

SECONDARY outcome

Timeframe: 2 months after intervention

Population: 55 randomized to PAP (2 dropout); 56 randomized to lifestyle (1 dropout)

Glucose effectiveness is the ability for glucose to move intracellularly in the absence of insulin. It is a parameter that results from the MINMOD analysis of the serum glucose and insulin levels derived from the frequently sampled intravenous glucose tolerance test. Low SG indicates a lower predisposition for glucose disposal independent of any effects of insulin.

Outcome measures

Outcome measures
Measure	Positive Pressure Therapy (PAP) n=53 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=55 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Glucose Effectiveness (SG)	0.01720 [min]^-1 Standard Deviation 0.01094	0.01385 [min]^-1 Standard Deviation 0.00636

SECONDARY outcome

Timeframe: Baseline

Population: 55 randomized to PAP (2 dropout); 56 randomized to lifestyle (1 dropout)

The disposition index is the mathematical product of insulin sensitivity (SI) and acute insulin response to glucose (AIRG) both of which are derived from the MINMOD analysis of the frequently sampled intravenous glucose tolerance test data. A low DI is indicative of a higher risk of developing diabetes.

Outcome measures

Outcome measures
Measure	Positive Pressure Therapy (PAP) n=53 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=55 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Disposition Index (DI)	931.4 [mU/L]^-1 x [min]^-1] x [mU/L-min] Standard Deviation 957.1	1093.1 [mU/L]^-1 x [min]^-1] x [mU/L-min] Standard Deviation 1037.9

SECONDARY outcome

Timeframe: 2 months after intervention

Population: 55 randomized to PAP (2 dropout); 56 randomized to lifestyle (1 dropout)

The disposition index is the mathematical product of insulin sensitivity (SI) and acute insulin response to glucose (AIRG) both of which are derived from the MINMOD analysis of the frequently sampled intravenous glucose tolerance test data.

Outcome measures

Outcome measures
Measure	Positive Pressure Therapy (PAP) n=53 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=55 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Disposition Index (DI)	1385.9 [mU/L]^-1 x [min]^-1] x [mU/L-min] Standard Deviation 1670.1	815.4 [mU/L]^-1 x [min]^-1] x [mU/L-min] Standard Deviation 579.5

SECONDARY outcome

Timeframe: Baseline

Population: 55 randomized to PAP (2 dropout); 56 randomized to lifestyle (1 dropout)

The acute insulin response to glucose (AIRG) value is derived from the MINMOD analysis of the glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test. A low AIRG indicates decreased ability of the pancreas to secrete insulin.

Outcome measures

Outcome measures
Measure	Positive Pressure Therapy (PAP) n=53 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=55 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Acute Insulin Response to Glucose (AIRG)	537.48 [mU/L-min] Standard Deviation 394.88	632.38 [mU/L-min] Standard Deviation 728.65

SECONDARY outcome

Timeframe: 2 months after intervention

Population: 55 randomized to PAP (2 dropout); 56 randomized to lifestyle (1 dropout)

The acute insulin response to glucose (AIRG) value is derived from the MINMOD analysis of the glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test. A low AIRG indicates decreased ability of the pancreas to secrete insulin.

Outcome measures

Outcome measures
Measure	Positive Pressure Therapy (PAP) n=53 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=55 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Acute Insulin Response to Glucose (AIRG)	513.06 [mU/L-min] Standard Deviation 338.41	563.64 [mU/L-min] Standard Deviation 546.20

SECONDARY outcome

Timeframe: Baseline

Population: Data was unable to be collected for all participants in this outcome measure.

Endothelial function will be assessed using peripheral arterial tonometry using the Endo-PAT device. Using the EndoPat device, the relative vasoconstriction of occluded versus non-occluded arms was derived and provided the relative hyperemic index.

Outcome measures

Outcome measures
Measure	Positive Pressure Therapy (PAP) n=49 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=54 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Endothelial Function	1.91 ratio of occluded versus non-occluded Standard Deviation 0.46	1.92 ratio of occluded versus non-occluded Standard Deviation 0.49

SECONDARY outcome

Timeframe: 2 month after intervention

Population: Data was not collected for all participants for this outcome measure. Participants for whom data was available are included in analysis.

Endothelial function will be assessed using peripheral arterial tonometry using the Endo-PAT device. Using the EndoPat device, the relative vasoconstriction of occluded versus non-occluded arms was derived and provided the relative hyperemic index.

Outcome measures

Outcome measures
Measure	Positive Pressure Therapy (PAP) n=49 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=54 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Endothelial Function	1.90 ratio Standard Deviation 0.53	1.91 ratio Standard Deviation 0.46

SECONDARY outcome

Timeframe: Baseline

Population: 55 randomized to PAP (2 dropout); 56 randomized to lifestyle (1 dropout)

Results of the oral glucose tolerance test will be analyzed using indices derived from the serial glucose and insulin levels over the 2 hour period. This will be the area under the glucose/ insulin curves

Outcome measures

Outcome measures
Measure	Positive Pressure Therapy (PAP) n=53 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=55 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Area Under the Curve Assessed by Oral Glucose Tolerance Test	7939.9 mg/dL per 120 min Standard Deviation 3327.8	7245.31 mg/dL per 120 min Standard Deviation 2988.4

SECONDARY outcome

Timeframe: 2 month after intervention

Population: 55 randomized to PAP (2 dropout); 56 randomized to lifestyle (1 dropout)

Results of the oral glucose tolerance test will be analyzed using indices derived from the serial glucose and insulin levels over a 2 hour period 2 months post intervention. This will be the area under the glucose/ insulin curves

Outcome measures

Outcome measures
Measure	Positive Pressure Therapy (PAP) n=53 Participants Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine. Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.	Lifestyle Counseling n=55 Participants Positive Pressure Therapy (PAP): Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep. LifeStyle Counseling: Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.
Area Under the Curve Assessed by Oral Glucose Tolerance Test (OGTT)	7531.8 mg/dL per 120 min Standard Deviation 3179.2	7655.1 mg/dL per 120 min Standard Deviation 3057.6

Adverse Events

Positive Pressure Therapy (PAP)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Lifestyle Counseling

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Naresh Punjabi

Johns Hopkins University

Phone: 410-550-6384

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place